HLA and autoimmunity in scleroderma (systemic sclerosis).
HLA and autoimmunity in scleroderma (systemic sclerosis).
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DOI：
10.3109/08830189509056707
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发表时间：
1995-01-01
影响因子：
5
通讯作者：
Arnett, F C
中科院分区：
文献类型：
--
作者：
Arnett, F C
硬皮病或系统性硬化症 (SSc) 与主要组织相容性复合物 (MHC) 的某些 II 类抗原有关，包括 HLA-DR1、DR2、DR3、DR5 和 DR52。一般来说，这些早期的 HLA 相关性很弱，并且在报告中心和不同种族人群之间差异很大。最近，已发现多种疾病特异性自身抗体，包括抗着丝粒、抗拓扑异构酶 I 和多种抗核仁抗体。这些特异性彼此之间几乎没有重叠，并且每一种都是 SSc 某些临床特征的标志。同时，MHC 的分子研究为定义特定 HLA 等位基因提供了更准确的方法。现在越来越清楚的是，某些 HLA II 类等位基因，尤其是 HLA-DQ，与 SSc 自身抗体亚群的相关性比与疾病本身的相关性更强。例如，抗着丝粒抗体与 HLA-DQB1*0501 (DQ5)、DQB1*0301 (DQ7) 和最外层结构域 26 位具有甘氨酸或酪氨酸残基的其他 DQB1 等位基因密切相关。抗拓扑异构酶 I 抗体出现在 HLA-DQB1*0301 (DQ7)、DQB1*0302 (DQ8)、DQB1*0601（日语为 DQ6）和其他在第 30 位具有酪氨酸残基的 DQB1 等位基因的 SSc 患者中。与这些自身抗体相关的 HLA-DQ 等位基因往往与自身抗体连锁不平衡。 HLA-DR 特异性以前与 SSc 本身关联较弱。罕见的 SSc 多重家族也显示出这些相同的 HLA 单倍型与受影响成员的自身抗体谱共分离。因此，MHC 等位基因似乎在影响 SSc 的血清学表达中发挥作用，并讨论了这些最新发现的含义。
Scleroderma or systemic sclerosis (SSc) has been associated with certain class II antigens of the major histocompatibility complex (MHC), including HLA-DR1, DR2, DR3, DR5, and DR52. In general, these earlier HLA correlations were weak and varied considerably among reporting centers and different ethnic populations. More recently, a variety of disease-specific autoantibodies have been discovered including anti-centromere, antitopoisomerase I, and a variety of anti-nucleolar antibodies. These specificities show little overlap among one another, and each are markers for certain clinical features of SSc. At the same time, molecular studies of the MHC have provided more accurate methods for defining specific HLA alleles. Now it is becoming clear that certain HLA class II alleles, especially HLA-DQ, are more strongly associated with autoantibody subsets of SSc than with the disease itself. For example, anticentromere antibodies are strongly associated with HLA-DQB1*0501 (DQ5), DQB1*0301 (DQ7) and other DQB1 alleles possessing a glycine or tyrosine residue in position 26 of the outermost domain. Anti-topoisomerase I antibodies occur in SSc patients with HLA-DQB1*0301 (DQ7), DQB1*0302 (DQ8), DQB1*0601 (DQ6 in Japanese), and other DQB1 alleles possessing a tyrosine residue in position 30. HLA-DQ alleles associated with these autoantibodies tend to be in linkage disequilibrium with the HLA-DR specificities previously associated weakly with SSc itself. Rare multiplex families with SSc also show these same HLA haplotypes co-segregating with autoantibody profiles in affected members. Thus, it appears that MHC alleles play a role in affecting the serological expression of SSc, and the implications of these recent findings are discussed.